B and T lymphocyte attenuator receptor (BTLA)

B and T lymphocyte attenuator receptor (BTLA, also known as CD272) is a type I transmembrane glycoprotein and a member of the CD28 immunoglobulin superfamily. It is expressed predominantly on lymphocytes (T and B cells) as well as some innate immune cells. BTLA is structurally and functionally related to other immune checkpoint receptors—such as PD-1 and CTLA-4—and contains both inhibitory and stimulatory signaling motifs in its cytoplasmic tail (ITIM, ITSM, and a Grb2-binding site). Its primary ligand is the herpesvirus entry mediator (HVEM), a member of the TNF receptor superfamily. BTLA functions as a co-inhibitory molecule that dampens immune cell activation and proliferation, thereby contributing to immune tolerance. Through these mechanisms, BTLA plays crucial roles in regulating tumor immunity, autoimmunity, infection responses, and transplant rejection. It is under active investigation as a target of immune-modulating therapies, though no approved drugs directly targeting BTLA are currently available.

Other names

CD272BTLA (abbreviation)B and T lymphocyte attenuator

Immune checkpoint inhibition: Drugs/antibodies targeting BTLA block or modulate its interaction with herpesvirus entry mediator (HVEM), thereby promoting T cell and immune activation against tumors or infection.\nImmune suppression: BTLA agonists could enhance its inhibitory signaling to suppress undesirable immune activation in autoimmunity or transplantation.\nKey intracellular signaling involves recruitment of SHP-1/SHP-2 (via ITIM/ITSM motifs), leading to inhibition of TCR-mediated signaling; also engagement of PI3K via Grb2 for cell survival/proliferation modulation.